In silico toxicologic profile and in vivo trypanocidal activity of estafietin, a sesquiterpene lactone isolated from Stevia alpina Griseb.

Abstract

Chagas disease is an infection caused by the protozoan Trypanosoma cruzi, affecting 6-8 million people worldwide. Only two drugs are available for its treatment, having a limited efficacy and adverse side-effects. Estafietin is a sesquiterpene lactone isolated from Stevia alpina with in vitro activity against T. cruzi and low cytotoxicity against mammalian cells. The aim of this work was to predict the toxicologic profile of estafietin by in silico methods and assess its in vivo activity on a murine model of Chagas disease. Estafietin showed low toxicity according to pkCSM web tool and passed the PAINS filter from PAINS-remover web server. The treatment of infected mice with 1 mg/Kg/day of estafietin for five consecutive days administrated by intraperitoneal route significatively decreased parasitemia levels and reduced inflammatory infiltrates and myocyte damage on muscle tissue. These results suggest that estafietin had effect both on acute and chronic stages of the infection.

GRAPHICAL ABSTRACT

Keywords:

• Sesquiterpene lactone
• estafietin
• Trypanosoma cruzi
• Chagas disease
• Stevia sp.

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability

The data used to support the findings of the study are included within the article. Additional data could be obtained upon request.

Additional information

Funding

This work was supported by the National Scientific and Technical Research Council (PIP 11220150100158CO), the National Agency for Scientific and Technological Promotion (PICT 2020-SERIEA-03061) and the University of Buenos Aires (UBACYT 20020170100316BA). This investigation is part of the activities within the “Research Network Natural Products against Neglected Diseases” (ResNet NPND): http://www.resnetnpnd.org/.